HLA and H-2 are the major histocompatibility systems (MHC) of man and mouse. Our approach to a study of new antigens and new loci, their function and map order, will be conducted on a well characterized donor panel and in families, some very large and with HLA related diseases, some with recombinant members. Simultaneous serologic and immunologic response examinations will use a variety of specific and sensitive techniques. To further understand the function and structure of MHC gene products, we will analyze histocompatibility mutations in mice, especially H-2K mutations. Additional studies will be directed toward a recognition and description of the alleles of differentiation antigens of T and B lymphocytes and macrophages and towards an understanding of their function. These studies will provide a more complete genetic basis for improving organ and tissue transplant matching and immunologic management; for reducing susceptibility to infections, malignant, and autoimmune diseases, and for understanding the immunogenetic factors that influence population structure.